Human immunodeficiency virus type 1 (HIV-1) exhibits a long clinical latent period between infection of individuals and the first evidence of disease. Unlike most other animal retroviruses, infection by HIV-1 does not result in high viremia and virus production in vivo. This suggests that the establishment of latent states in infected cells may be important in HIV-1 pathogenesis. In this proposal, in vitro HIV-1 persistence/latency will be investigated. Model systems will be developed, using primary human T-lymphocytes and a molecularly cloned primary isolate of HIV-1. These models will be used in conjunction with highly sensitive molecular techniques to investigate the molecular nature of HIV-1 in the latent state and following reactivation. These studies will allow the development of new assays and the understanding of viral targets for potential therapeutic agents.